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Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions.

Balhana RJ, Singla A, Sikder MH, Withers M, Kendall SL - BMC Genomics (2015)

Bottom Line: We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes.Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps.TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. r.balhana@surrey.ac.uk.

ABSTRACT

Background: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria.

Results: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs.

Conclusion: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.

No MeSH data available.


Related in: MedlinePlus

Lengths of the intergenic regions of the divergently oriented mycobacterial TFTR regulators. The intergenic regions from the 422 divergently oriented regulators from M. tuberculosis (Mtb), M. avium paratuberculosis (MAP), M. marinum (MM), M. ulcerans (MUL), M. gilvum (MGIL) and M. smegmatis (MSM) were analysed for length. Each dot represents an intergenic region and the length is given on the y-axis. Each of the genes were assigned a number e.g. 1–33 for MTB, 34–97 for MAP, 98–174 for MM, 175–225 for MUL, 226–312 for MGIL and 313–422 for MSMEG. The assignation of number was done in gene number order in each organism e.g. 1 = Rv0067c, 2 = Rv0078, 3 = Rv0135c etc. and this is given on the x-axis. The line represents a cut-off intergenic region size of 200 bp. The graph shows that the majority of divergently oriented genes are separated from their neighbour by 200 bp or less
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Fig3: Lengths of the intergenic regions of the divergently oriented mycobacterial TFTR regulators. The intergenic regions from the 422 divergently oriented regulators from M. tuberculosis (Mtb), M. avium paratuberculosis (MAP), M. marinum (MM), M. ulcerans (MUL), M. gilvum (MGIL) and M. smegmatis (MSM) were analysed for length. Each dot represents an intergenic region and the length is given on the y-axis. Each of the genes were assigned a number e.g. 1–33 for MTB, 34–97 for MAP, 98–174 for MM, 175–225 for MUL, 226–312 for MGIL and 313–422 for MSMEG. The assignation of number was done in gene number order in each organism e.g. 1 = Rv0067c, 2 = Rv0078, 3 = Rv0135c etc. and this is given on the x-axis. The line represents a cut-off intergenic region size of 200 bp. The graph shows that the majority of divergently oriented genes are separated from their neighbour by 200 bp or less

Mentions: For those that are divergently transcribed, the majority of regulators are separated from their divergent partners by 200 bp or less (Fig. 3). So, for M. tuberculosis 25 out of the 33 divergently oriented genes are separated by 200 bp or less (76 %) and such high frequencies are also observed in the rest of the mycobacteria (53/64 for M. avium paratuberculosis (83 %), 58/77 for M. marinum (75 %), 34/51 for M. ulcerans (67 %), 74/87 for M. gilvum (85 %) and 96/110 for M. smegmatis (87 %). These analyses suggest that the majority of the divergently oriented TFTRs can be predicted to regulate the adjacent gene.Fig. 3


Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions.

Balhana RJ, Singla A, Sikder MH, Withers M, Kendall SL - BMC Genomics (2015)

Lengths of the intergenic regions of the divergently oriented mycobacterial TFTR regulators. The intergenic regions from the 422 divergently oriented regulators from M. tuberculosis (Mtb), M. avium paratuberculosis (MAP), M. marinum (MM), M. ulcerans (MUL), M. gilvum (MGIL) and M. smegmatis (MSM) were analysed for length. Each dot represents an intergenic region and the length is given on the y-axis. Each of the genes were assigned a number e.g. 1–33 for MTB, 34–97 for MAP, 98–174 for MM, 175–225 for MUL, 226–312 for MGIL and 313–422 for MSMEG. The assignation of number was done in gene number order in each organism e.g. 1 = Rv0067c, 2 = Rv0078, 3 = Rv0135c etc. and this is given on the x-axis. The line represents a cut-off intergenic region size of 200 bp. The graph shows that the majority of divergently oriented genes are separated from their neighbour by 200 bp or less
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482099&req=5

Fig3: Lengths of the intergenic regions of the divergently oriented mycobacterial TFTR regulators. The intergenic regions from the 422 divergently oriented regulators from M. tuberculosis (Mtb), M. avium paratuberculosis (MAP), M. marinum (MM), M. ulcerans (MUL), M. gilvum (MGIL) and M. smegmatis (MSM) were analysed for length. Each dot represents an intergenic region and the length is given on the y-axis. Each of the genes were assigned a number e.g. 1–33 for MTB, 34–97 for MAP, 98–174 for MM, 175–225 for MUL, 226–312 for MGIL and 313–422 for MSMEG. The assignation of number was done in gene number order in each organism e.g. 1 = Rv0067c, 2 = Rv0078, 3 = Rv0135c etc. and this is given on the x-axis. The line represents a cut-off intergenic region size of 200 bp. The graph shows that the majority of divergently oriented genes are separated from their neighbour by 200 bp or less
Mentions: For those that are divergently transcribed, the majority of regulators are separated from their divergent partners by 200 bp or less (Fig. 3). So, for M. tuberculosis 25 out of the 33 divergently oriented genes are separated by 200 bp or less (76 %) and such high frequencies are also observed in the rest of the mycobacteria (53/64 for M. avium paratuberculosis (83 %), 58/77 for M. marinum (75 %), 34/51 for M. ulcerans (67 %), 74/87 for M. gilvum (85 %) and 96/110 for M. smegmatis (87 %). These analyses suggest that the majority of the divergently oriented TFTRs can be predicted to regulate the adjacent gene.Fig. 3

Bottom Line: We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes.Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps.TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. r.balhana@surrey.ac.uk.

ABSTRACT

Background: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria.

Results: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs.

Conclusion: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.

No MeSH data available.


Related in: MedlinePlus